Opioid dependence is a serious public health problem whose severity is magnified due to its association with IV drug use and AIDS. The United States is actively pursuing approval of promising new treatment alternatives such as buprenorphine to combat opioid dependence. In this application, we propose to extend previous successes with buprenorphine to a large urban environment with significant numbers of untreated addicts. Specifically, we will examine a promising new combination buprenorphine-naloxone tablet in five clinical pharmacology studies and one maintenance study. We propose to answer six questions across three experiments over three years. Experiment I extends our research on alternative buprenorphine dosing schedules which demonstrated that subjects can safely receive buprenorphine every other day or every three days by doubling or tripling buprenorphine doses. These dosing schedules may eliminate the need for take-home medication for patients who need days off from the clinic. Experiment I addresses two questions. Study 1 determines whether a combination buprenorphine-naloxone tablet can be administered safely and effectively every other day and whether multiples of the daily dose are essential. Study 2 examines treatment outcome with a combination buprenorphine-naloxone tablet by comparing daily to 3-day dosing schedules with and without take-home doses. Experiment II examines the abuse liability of combination buprenorphine-naloxone tablets in three populations of opioid abusers to determine if the combination reduces parenteral abuse of buprenorphine. Experiment II addresses three questions. Study 1 determines the abuse liability of the combination buprenorphine-naloxone tablet in buprenorphine-maintained patients. Study 2 determines the abuse liability of the combination buprenorphine- naloxone tablet in opioid-dependent individuals not seeking treatment. Study 3 determines the abuse liability of the combination buprenorphine- naloxone tablet in non-dependent opioid abusers. Experiment III determines the clinical efficacy of the combination buprenorphine- naloxone tablet for short-term maintenance treatment by comparing two doses of the combination buprenorphine-naloxone tablet and two doses of methadone during a 16-week randomized trial. Overall, this research provides essential pragmatic guidance for practitioners and scientists about the clinical use of the combination buprenorphine-naloxone tablet thereby permitting the tablet to be used with the greatest efficacy in clinical settings. Moreover, these studies will extend prior findings and improve drug abuse treatment by providing important information about a newly-developed combination buprenorphine-naloxone tablet in a wide range of individuals, including those who have not been exposed to methadone and/or other treatments for opioid dependence problems.